title: Recombinant lipoproteins reinforce cytotoxicity of doxorubicin to hepatocellular carcinoma.
abstract: Cancer nanotherapeutics are changing the landscape of tumor treatment and used to circumvent limitations of conventional chemotherapy, such as non-specificity and low bioavailability. Reconstituted high density lipoproteins (rHDL) system is one of the most promising targeting delivery systems of chemotherapeutic drugs toward tumors. Here, we developed recombined high-density lipoprotein which can be functionalized to deliver doxorubicin intracellular with a higher efficiency. The cellular viability assay showed that the rHDL/Dox nanovectors had an enhanced efficiency in inhibiting the cell viability of hepatocellular carcinoma cell lines HepG2 and SMMC-7721. FACS and confocal microscopy was used to observe the doxorubicin delivery into cancer cells. Intracellular drug accumulation analysis confirmed that treatment of rHDL/Dox nanovectors resulted in higher intracellular doxorubicin concentration to the levels exceeding that of free drug. On the premise of efficient drug delivery, rHDL/Dox nanovectors have been preliminarily demonstrated effective inducing of cytotoxic effect and cell apoptosis to both of the cell lines in vitro. Tissue distribution experiment showed that rHDL/Dox nanovectors could also deliver doxorubicin to liver effectively. So, we proposed that this lipoprotein-based strategy holds promise for a safer and more efficient delivery of chemotherapeutic agents in the treatment of hepatocellular carcinoma.
authors.affiliation: School of Pharmacy, Fudan University , Shanghai , China.
authors.forename: Baolong
authors.initials: B
authors.lastname: Wang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.forename: Lei
authors.initials: L
authors.lastname: Han
authors.forename: Li
authors.initials: L
authors.lastname: Ye
authors.forename: Xunlong
authors.initials: X
authors.lastname: Shi
authors.forename: Meiqing
authors.initials: M
authors.lastname: Feng
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D056945:Hep G2 Cells; D006801:Humans; D008075:Lipoproteins, HDL / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000494:pharmacology*; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008075:Lipoproteins, HDL; D011994:Recombinant Proteins; D004317:Doxorubicin